Process for production of 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivatives

ABSTRACT

A process for the production of a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative of formula (2): 
                         
wherein R is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted aralkyl, which process comprises reacting a 3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acid compound of formula (1):
 
                         
wherein R is as defined above, with a periodic acid compound in the presence of a ruthenium compound.

TECHNICAL FIELD

The present invention relates to a process for the production of3,3-dimethyl-2-formylcyclopropanecarboxlic acid derivatives.

BACKGROUND ART

The 3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acidcompounds of formula (1):

wherein R is hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aryl, or substituted or unsubstituted aralkyl, are veryimportant compounds as the intermediate for the synthesis ofpyrethroid-type household agents for epidemic prevention, pesticides, orthe like. There have also been developed a number of analogs in whichthe 2-methyl-1-propenyl groups attached to the cyclopropane rings arereplaced with various alkenyl groups, using the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acid compoundof the above formula (1) as the key compound, as well as a number ofhousehold agents for epidemic prevention, pesticides, and the like usingthese analogs.

As the process for producing the analogs in which the2-methyl-1-propenyl groups attached to the cyclopropane rings arereplaced with various alkenyl groups, there has been known, for example,a process in which the 3,3-dimethyl-2-formylcyclopropanecarboxylic acidderivative of formula (2):

wherein R is as defined above, are reacted with Wittig reagents (see,e.g., J. Labelled Compounds and Radiopharmaceuticals, 13, 561(1977)).The 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivatives of theabove formula (2) become important compounds in the synthesis of theabove analogs.

As the processes for the production of the3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative of formula(2), there have been known, for example, a process in which the3,3-dimethyl-2-(2-methyl-1-propenyl)-cyclopropanecarboxylic acidcompound of the above formula (1) are oxidized in the presence of anosmium tetroxide catalyst (see, e.g., J. Labelled Compounds andRadiopharmaceuticals, 13, 561(1977)) and a process in which the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acidcompounds of the above formula (1) are oxidized with ozone (see, e.g.,JP-B 46-24695). However, since the former process uses highly toxicosmium tetroxide and the latter process has a tendency to needlarge-scale equipment, both cannot be said to be production processessuitable on an industrial scale.

Journal of the Chemical Society, Perkin Transactions I, 1980 pages1711-1717 discloses a process for preparingcis-2,2-formyl-3,3-diemethylcyclopropanecarboxylate by oxidizing achrysanthemate with sodium metaperiodate in the presence of thecatalyst, osmium tetraoxide. However, this process also uses highlytoxic osmium tetroxide and cannot be said to be a process suitable on anindustrial scale. EP-A 0 444 708 discloses a process for preparing aketone or aldehyde compound by oxidizing an olefin compound having aβ-lactam structure. JP-A 5-229981 discloses a process for preparing anaromatic acetaldehyde by oxidizing an allyl substituted aromaticcompound with sodium periodate in the presence of a ruthenium catalystand a phase transfer catalyst. JP-A 55-087739 discloses a process forpreparing an aromatic aldehyde by oxidizing an α, β unsaturated aromaticcompound in the presence of an oxidizing agent and a ruthenium catalyst.However, the oxidization disclosed in these processes are not comparedto the above oxidization of the compound of the above formula (1).

DISCLOSURE OF THE INVENTION

Under these circumstances, the present inventor has intensively studieda process for the production of the3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative of the aboveformula (2) on an industrial scale and has found that the desired3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivatives of formula(2) can be obtained in good yield by reacting the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acidcompounds of the above formula (1) with a periodic acid compound in thepresence of a ruthenium compound, thereby completing the presentinvention.

Thus the present invention provides a process for the production of a3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative of formula(2):

wherein R is hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aryl, or substituted or unsubstituted aralkyl, whichprocess comprises reacting a3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acid compoundof formula (1):

wherein R is as defined above, with a periodic acid compound in thepresence of a ruthenium compound.

MODE FOR CARRYING OUT THE INVENTION

In the formula for the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acidcompounds of formula (1):

(hereinafter abbreviated as carboxylic acid compounds (1)), R representshydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted aryl, or substituted or unsubstituted aralkyl.

The unsubstituted alkyl may include, for example, straight or branchedchain, or cyclic alkyl groups of 1 to 10 carbon atoms, such as methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,n-pentyl, cyclopentyl, n-hexyl, cyclohexyl, and menthyl, and thesubstituted alkyl may include alkyl groups substituted with asubstituent(s) such as halogen atoms (e.g., fluorine, chlorine,bromine), alkoxy groups (e.g., C₁-C₄ alkoxy such as methoxy, ethoxy,n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert-butoxy), aryloxygroups (eg., phenoxy), or aralkyloxy groups (e.g., benzyloxy), whichsubstituted alkyl groups may include, for example, 2-chloroethyl,2-fluoroethyl, pentafluoroethyl, 2-methoxyethyl, 2-ethoxyethyl,2-phenoxyethyl, and 2-(benzyloxy)ethyl.

The unsubstituted aryl may include, for example, phenyl and naphthylgroups, and the substituted aryl may include phenyl and naphthyl groupssubstituted with a substituent(s), such as the above substituted orunsubstituted alkyl, the above alkoxy, the above aryloxy, and/or theabove aralkyloxy. Examples of the substituted phenyl and naphthyl groupsmay include, for example, 2-chlorophenyl, 4-fluorophenyl,2-methylphenyl, 4-methoxyphenyl, and 4-phenoxyphenyl.

The substituted or unsubstituted aralkyl may include, for example, thosewhich are composed of the above substituted or unsubstituted alkylgroups and the above substituted or unsubstituted aryl groups, such asbenzyl, phenylethyl, chlorobenzyl, methylbenzyl, methoxybenzyl,phenoxybenzyl, 2,3,5,6-tetrafluorobenzyl,2,3,5,6-tetrafluoro-4-methylbenzyl, 2,3,5,6-tetrafluoro-4-methoxybenzyl,and 2,3,5,6-tetrafluoro-4-methoxybmethylbenzyl.

The carboxylic acid compound (1) may include3,3-diemthyl-2-(2-methyl-1-propenyl)cyclopropane carboxylic acid, methyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, ethyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, n-propyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, isopropyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, n-butyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, isobutyl3,3-dimethyl-2-(2-methyl-1-propenyl)-cyclopropanecarboxylate, tert-butyl3,3-dimethyl-2-(2-methyl-1-propenyl)-cyclopropanecarboxylate, phenyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, 1-naphthyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, 2-naphthyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, benzyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate,2,3,5,6-tetrafluorobenzyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate,2,3,5,6-tetrafluoro-4-methylbenzyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate,2,3,5,6-tetrafluoro-4-methoxybenzyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and2,3,5,6-tetrafluoro-4-methoxymethylbenzyl3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate.

The carboxylic acid compound (1) contain two asymmetric carbon atoms intheir molecules, and provide four kinds of isomers. In the presentinvention, either any one of these isomers or a mixture of these isomerscan be used.

The ruthenium compound may include, for example, ruthenium metal;ruthenium oxides such as ruthenium (IV) oxide; ruthenium halides such asruthenium (III) chloride and ruthenium (III) bromide; rutheniumcomplexes such as tris(acetylacetonato)ruthenium (III),bis(cydopentadien-yl)ruthenium (II),bis(pentamethylcyclopentadienyl)ruthenium (II),dichloro-(p-cymene)ruthenium (II) diner,dichloro(1,5-cyclooctadiene)ruthenium (II) dimer, benzeneruthenium (II)chloride dimer, tris(2,2′-bipyridyl)dichloro-ruthenium (II),dichlorotris(triphenylphosphine)ruthenium (II),carbonyldihydridotris(triphenylphosphine)ruthenium (II), andtriruthenium dodecacarbonyl (0); and perruthenates such astetra(n-propyl)ammonium perruthenate (VII).

These ruthenium compounds may be those which are supported on activecarbon, silica, alumina, or the like. In the case of ruthenium oxides orruthenium halides, their hydrates are usually used.

The amount of ruthenium compound that may be suitably used is usually0.05 mol % or higher, preferably 0.1 mol % or higher, per mol of thecarboxylic acid compound (1), and there is no upper limit thereof. Toohigher amounts have a tendency to become disadvantageous from aneconomical point of view, and therefore, in practical cases, the amountof ruthenium compound that may be suitably used is not higher than 10mol %, preferably not higher than 5 mol %.

The periodic acid compounds may be those which exhibit acidic propertyin their aqueous solutions, and may include periodic acid (H₅IO₆),sodium metaperiodate (NaIO₄), and potassium metaperiodate (KIO₄). Theperiodic acid compounds which exhibit neutral to alkaline property intheir aqueous solutions, such as lithium periodate (LiIO₄), sodiumparaperiodate (Na₂H₃IO₆, Na₃H₂IO₆), and potassium dimesoperiodate(K₄I₂O₆), can be used in the present invention by reacting in advancewith an aqueous solution of an acid such as sulfuric acid or nitric acidto convert them into a periodic acid compound which exhibits acidicproperty in their aqueous solutions. Alternatively, periodic acidcompounds which exhibit neutral to alkaline property in their aqueoussolutions are mixed in advance with carboxylic acid compound (1), and anaqueous solution of an acid such as sulfuric acid or nitric acid isadded to make the reaction system acidic, thereby producing periodicacid compounds which exhibit acidic property in their aqueous solutionsand carrying out the reaction.

For some of these periodic acid compounds, there may exist theirhydrates, and in the present invention, either anhydrates or hydratesmay be used.

The amount of the periodic acid compound that may be suitably used isusually not lower than 2 moles, per mol of the carboxylic acid compound(1), and there is no upper limit thereof. Too higher amounts have atendency to cause further oxidation of the desired product, andtherefore, in practical cases, the amount of the periodic acid compoundthat may be suitably used is not higher than 5 moles, preferably nothigher than 3 moles, per mol of the carboxylic acid compound (1).

The reaction of the carboxylic acid compound (1) with the periodic acidcompound is usually carried out in water or a mixture of awater-immiscible organic solvent and water. The water-immiscible organicsolvent may include aromatic hydrocarbon solvents such as toluene,xylene, mesitylene, and chlorobenzene; aliphatic hydrocarbon solventssuch as pentane, hexane, heptane, octane, and cyclohexane; estersolvents such as ethyl acetate; ketone solvents such as methyl isobutylketone and methyl ethyl ketone; and halogenated aliphatic hydrocarbonsolvents such as dichloromethane, dichloroethane, and carbontetrachloride. Preferred is a mixture of water and the water-immiscibleorganic solvent. The amount for its use is usually not lower than 2parts by weight, preferably not lower than 5 parts by weight, per 1 partby weight of the carboxylic acid compound (1). There is no upper limitthereof, but taking into consideration volume efficiency and the like,the amount for its use in practical cases is not higher than 100 partsby weight, per 1 part by weight of the carboxylic acid compound (1).When a mixture of water and the water-immiscible organic solvent isused, there is no particular limitation on the mixing ratio of the waterand the water-immiscible organic solvent.

The reaction temperature is usually −10° C. to 50° C., preferably −5° C.to 15° C.

The reaction may usually be effected only by mixing and contacting ofcarboxylic acid compound (1), a ruthenium compound, and a periodic acidcompound. There is no particular limitation on the order of mixing.

After completion of the reaction, when the reaction mixture containsinsoluble matter, for example, the filtration of the insoluble matter,followed by phase separation, gives an organic layer containing thedesired 3,3,-dimethyl-2-formylcyclopropanecarboxylic acid derivative offormula (2):

wherein R is as defined above (hereinafter abbreviated as carboxylicacid derivative (2)). Alternatively, the reaction mixture isheat-treated, and in necessary, water, or water and a water-immiscibleorganic solvent is added so that some or all of the insoluble matter isdissolved, followed by filtration and/or phase separation, thusobtaining an organic layer containing the carboxylic acid derivative(2). For the heat treatment of the reaction mixture, the reactionmixture may be heat-treated as such or after the adjustment of pH toaround neutral from the viewpoint of controlling the formation ofby-products by the heat treatment.

When the reaction mixture contains no insoluble matter, if necessary,water and/or a water-immiscible organic solvent are added to theresulting reaction mixture, followed by phase separation, thus obtainingan organic layer containing carboxylic acid derivative (2).

The carboxylic acid derivative (2) can be isolated by washing, ifnecessary, the organic layer containing the carboxylic acid derivative(2) with an aqueous solution of sodium thiosulfate or the like, followedby concentration. The isolated carboxylic acid derivative (2) mayfurther purified by ordinary means of purification, such as distillationor chromatography.

When the reaction mixture contains the remaining periodic acidcompounds, it may be mixed with an inorganic reducing agent such assodium sulfite, sodium thiosulfate, or sodium hydrogensulfite; a primaryalcohol such as methanol or ethanol; a secondary alcohol such asisopropyl alcohol, or the like to attain the reduction of the remainingperiodic acid compounds, followed by the above treatment.

Depending on the kind of ruthenium catalyst used, the catalyst mayremain dissolved in the reaction mixture, in which case the reactionmixture may be mixed with an adsorbent such as active carbon to removethe catalyst by adsorption.

The filtered insoluble matter or the aqueous layer obtained by phaseseparation contains iodic acid compound formed as by-products(hereinafter abbreviated as by-product iodic acid compounds) in thereaction of carboxylic acid compounds (1) with periodic acid compounds.The conversion of by-product iodic acid compounds into periodic acidcompounds to reuse in the present invention is preferred from aneconomical point of view and from the viewpoint of environmental burdenbecause of a reduction in iodine-containing waste products. For example,when sodium metaperiodate (NaIO₄) is used as a periodic acid compound,sodium iodate and/or iodic acid are formed as by-product iodic acidcompounds.

As a method for converting by-product iodic add compounds into periodicacid compounds, for example, the by-product iodic add compounds arereacted with an oxidizing agent in the presence of an alkali to convertthem into periodic acid compounds which exhibit alkaline property intheir aqueous solutions, followed by treatment with an acid such assulfuric acid or nitric acid, to convert them into periodic addcompounds which exhibit acidic property in their aqueous solutions.

The oxidizing agent may include hypohalites such as sodium hypochlorite;halogens such as chlorine and bromine; and peroxodisulfates such aspotassium peroxodisulfate. The amount for its use is usually 1 to 3moles, per mol of the by-product iodic acid compounds. The alkali mayinclude alkali metal hydroxides such as sodium hydroxide and potassiumhydroxide. The amount for its use is usually 0.5 to 3 moles, per mol ofthe by-product iodic acid compounds. The alkali is usually used as anaqueous solution.

The reaction temperature in the reaction of by-product iodic acidcompounds with an oxidizing agent is usually 50° C. to 100° C.

When the above insoluble matter (by-product iodic acid compounds) isreacted with an oxidizing agent, the reaction is usually carried out inwater. The amount of water used is usually 2 to 10 parts by weight, per1 part by weight of the insoluble matter. When the aqueous layercontaining by-product iodic acid compounds is reacted with an oxidizingagent, both may usually be brought into contact with each other andmixed as such, and if necessary, water may be added.

The following will specifically explain, taking as an example the casewhere the by-product iodic acid compound is sodium iodate. The sodiumiodate formed as a by-product is usually reacted with an oxidizing agentsuch as sodium hypochlorite in water in the presence of an alkali suchas sodium hydroxide, so that sodium paraperiodate which exhibitsalkaline property in its aqueous solution is usually deposited ascrystals. For sodium paraperiodate, there exist two types, ie., Na₂H₃IO₆and Na₃H₂IO₆. The suitable selection of reaction conditions includingthe amount of alkali and the pH of the reaction mixture can selectivelygive any one of Na₂H₃IO₆ and Na₃H₂IO₆. Therefore, the reactionconditions may be selected, depending on the kind of the desired sodiumparaperiodate. Taking into consideration the amount of alkali used, theamount of acid used for the conversion into sodium metaperiodate, andthe like, the recovery as Na₂H₃IO₆ is advantageous and preferred from aneconomical point of view.

The deposited crystals of sodium paraperiodate are removed byfiltration, and if necessary, subjected to washing, followed bytreatment with an acid such as nitric acid or sulfuric acid, to convertinto sodium metaperiodate (NaIO₄). The sodium metaperiodate (NaIO₄)obtained may be isolated and reused for the reaction of the abovecarboxylic acid compound (1) with the periodic acid compound, or may bereused, without separation, for example, as an aqueous solution orsuspension containing sodium metaperiodate (NaIO₄) obtained by treatmentwith an acid, for the reaction of the above carboxylic acid compounds(1) with the periodic acid compound.

When the iodic acid compound formed as a by-product is potassium iodate,potassium iodate formed as a by-product is reacted with an oxidizingagent such as chlorine in an aqueous solvent in the presence of analkali such as potassium hydroxide to convert into potassiumdimesoperiodate (K₄I₂O₉), followed by treatment with an acid such asnitric acid, so that potassium metaperiodate (KIO₄) can usually berecovered as crystals.

The carboxylic acid derivative (2) thus obtained may include3,3-dimethyl-2-formylcyclopropanecarboxylic acid, methyl3,3-dimethyl-2-formylcyclopropanecarboxylate, ethyl3,3-dimethyl-2-formylcyclopropanecarboxylate, n-propyl3,3-dimethyl-2-formylcyclopropanecarboxylate, isopropyl3,3-dimethyl-2-formylcyclopropanecarboxylate, n-butyl3,3-dimethyl-2-formylcyclopropanecarboxylate, isobutyl3,3-dimethyl-2-formylcyclopropanecarboxylate, tert-butyl3,3-dimethyl-2-formylcyclopropanecarboxylate, phenyl3,3-dimethyl-2-formylcyclopropanecarboxylate, 1-naphthyl3,3-dimethyl-2-formylcyclopropanecarboxylate, 2-naphthyl3,3-dimethyl-2-formylcyclopropanecarboxylate, benzyl3,3-dimethyl-2-formylcyclopropanecarboxylate, 2,3,5,6-tetrafluorobenzyl3,3-dimethyl-2-formylcyclopropanecarboxylate,2,3,5,6-tetrafluoro-4-methylbenzyl3,3-dimethyl-2-formylcyclopropanecarboxylate,2,3,5,6-tetrafluoro-4-methoxybenzyl3,3-dimethyl-2-formylcyclopropanecarboxylate, and2,3,5,6-tetrafluoro-4-methoxymethylbenzyl3,3-dimethyl-2-formylcyclopropanecarboxylate.

EXAMPLES

The present invention will hereinafter be further illustrated by thefollowing Examples; however, the present invention is not limited tothese Examples. In the Examples, the analysis was carried out by gaschromatography (the internal standard method).

Example 1

To 44.4 g of sodium paraperiodate (Na₂H₃IO₆) was added 195 g of waterand at an internal temperature of 25° C. was added 17.2 g of 60 wt. %nitric acid, giving an aqueous solution containing sodium metaperiodate(NaIO₄). To the aqueous solution was further added 1.7 g of sodiummetaperiodate (NaIO₄), followed by adjustment to an internal temperatureof 0° C. Then, 32.6 mg of ruthenium chloride (III) hydrate, 14.2 g ofmethyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and141 g of toluene were added, and the mixture was stirred at the sametemperature for 23.5 hours to effect reaction. After completion of thereaction, 2.2 g of isopropyl alcohol was added to reduce the remainingsodium metaperiodate (NaIO₄), followed by the addition of an aqueoussolution of 20 wt. % sodium carbonate for neutralization.

At an internal temperature of 70° C., 0.4 g of active carbon was added,and the mixture was stirred for about 30 minutes, followed by filtrationat the same temperature. The filtrate was left at rest, followed byphase separation to give an organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate and an aqueous layercontaining by-product sodium iodate and/or iodic acid. The organic layerwas washed with an aqueous solution of sodium thiosulfate, followed byconcentration under reduced pressure to give 26.9 g (content: 38.8 wt.%) of concentrated residue containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 86%.

Further, 274 g of the above aqueous layer was concentrated under reducedpressure to remove the acetone and isopropyl alcohol contained, followedby dropwise addition of 26.9 g of a 30 wt. % aqueous solution of sodiumhydroxide and 109.5 g of a 12.8 wt. % aqueous solution of sodiumhypochlorite at an internal temperature of 80° C., and the mixture wasstirred at the same temperature for 4 hours to effect reaction. Then,the mixture was cooled to an internal temperature of 30° C. or lower, towhich 60 wt. % nitric acid was added for the adjustment to pH 6. Thedeposited crystals were removed by filtration and dried under reducedpressure to give 46.1 g of sodium paraperiodate (Na₂H₃IO₆). The rate ofrecovery to the sodium paraperiodate and sodium metaperiodate used abovewas 99%.

Example 2

To 26.3 g of sodium paraperiodate (Na₂H₃IO₆) was added 58 g of water andat an internal temperature of 65° C. was added 10.1 g of 60 wt. % nitricacid, giving an aqueous solution containing sodium metaperiodate(NaIO₄). After the adjustment to an internal temperature of 0° C., 12.5mg of ruthenium oxide (IV) hydrate, 8 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and80 g of toluene were added, and the mixture was stirred at the sametemperature for 23 hours to effect reaction. After completion of thereaction, 1.8 g of isopropyl alcohol was added to reduce the remainingsodium metaperiodate (NaIO₄), followed by the addition of a 20 wt. %aqueous solution of sodium carbonate for neutralization.

At an internal temperature of 0° C., insoluble matter containingby-product sodium iodate was removed by filtration. The removedinsoluble matter was washed with toluene, and the washing solution wasmixed with the filtrate previously obtained. The filtrate after themixing was subjected to phase separation, and the resulting organiclayer washed with an aqueous solution of sodium thiosulfate to give110.3 g (content: 5.5 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 88%.

Example 3

To 26.3 g of sodium paraperiodate (Na₂H₃IO₆) was added 58 g of water andat an internal temperature of 65° C. was added 10.1 g of 60 wt. % nitricacid, giving an aqueous solution containing sodium metaperiodate(NaIO₄). After the adjustment to an internal temperature of 0° C., 178.9mg of 5 wt. % ruthenium/alumina, 8 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and80 g of toluene were added, and the mixture was stirred at the sametemperature for 28 hours to effect reaction. After completion of thereaction, 1.8 g of isopropyl alcohol was added to reduce the remainingsodium metaperiodate (NaIO₄), followed by the addition of a 20 wt. %aqueous solution of sodium carbonate for neutralization.

At an internal temperature of 0° C., insoluble matter containingby-product sodium iodate was removed by filtration. The removedinsoluble matter was washed with toluene, and the washing solution wasmixed with the filtrate previously obtained. The filtrate after themixing was subjected to phase separation, and the resulting organiclayer washed with an aqueous solution of sodium thiosulfate to give124.7 g (content: 4.9 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 89%.

Example 4

To 13.5 g of sodium paraperiodate (Na₂H₃IO₆) was added 30 g of water andat an internal temperature of 65° C. was added 5.3 g of 60 wt. % nitricacid, giving an aqueous solution containing sodium metaperiodate(NaIO₄). After the adjustment to an internal temperature of 0° C., 91 mgof 5 wt. % ruthenium/active carbon, 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and41 g of toluene were added, and the mixture was stirred at the sametemperature for 21 hours to effect reaction. After completion of thereaction, 1.2 g of isopropyl alcohol was added to reduce the remainingsodium metaperiodate (NaIO₄), followed by the addition of a 20 wt. %aqueous solution of sodium carbonate for neutralization.

At an internal temperature of 0° C., insoluble matter containingby-product sodium iodate was removed by filtration. The removedinsoluble matter was washed with toluene, and the washing solution wasmixed with the filtrate previously obtained. The filtrate after themixing was subjected to phase separation, and the resulting organiclayer washed with an aqueous solution of sodium thiosulfate to give 69.5g (content: 4.4 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 87%.

Example 5

To 10.8 g of sodium metaperiodate (NaIO₄) was added 33 g of water, andthe mixture was adjusted to an internal temperature of 0° C., followedby the addition of 10.4 mg of bis(cyclopentadienyl)ruthenium (II). Tothis were added 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 21g of toluene, and the mixture was stirred at an internal temperature of0° C. for 8 hours to effect reaction. After completion of the reaction,insoluble matter containing by-product sodium iodate was removed byfiltration. The removed insoluble matter was washed with toluene, andthe washing solution was mixed with the filtrate previously obtained.The filtrate after the mixing was subjected to phase separation, and theresulting organic layer washed with an aqueous solution of sodiumthiosulfate to give 55.2 g (content: 5.9 wt. %) of the organic layercontaining methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.The yield was 91%.

Example 6

In the same manner as described in Example 5, except that 13.4 mg ofdichloro(p-cymene) ruthenium (II) dimer was used in place of 10.4 mg ofbis(cyclopentadienyl)ruthenium (II) and the reaction time was set to 9hours, 54.5 g (content: 5.4 wt. %) of the organic layer containingmethyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was83%.

Example 7

In the same manner as described in Example 5, except that 5.5 mg ofbenzeneruthenium (II) chloride dimer was used in place of 10.4 mg ofbis-(cyclopentadienyl)ruthenium (II) and the reaction time was set to 12hours, 54.7 g (content: 5.3 wt. %) of the organic layer containingmethyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was82%.

Example 8

In the same manner as described in Example 5, except that 42 mg ofdichlorotris(triphenylphosphine)ruthenium (I) was used in place of 10.4mg of bis(cyclopentadienyl)ruthenium (II), 52.2 g (content: 5.6 wt. %)of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 82%.

Example 9

In the same manner as described in Example 5, except that 18.1 mg oftris(acetylacetonato)ruthenium (II) was used in place of 10.4 mg ofbis-(cyclopentadienyl)ruthenium (II) and the reaction time was set to 11hours, 52.4 g (content: 5.7 wt. %) of the organic layer containingmethyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was85%.

Example 10

In the same manner as described in Example 5, except that 41.5 mg ofcarbonyldihydridotris(triphenylphosphine)ruthenium (II) was used inplace of 10.4 mg of bis(cyclopentadienyl)ruthenium (II) and the reactiontime was set to 7 hours, 58.9 g (content: 5.0 wt. %) of the organiclayer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 84%.

Example 11

In the same manner as described in Example 5, except that 15.4 mg oftetra(n-propyl)ammonium perruthenate (VII) was used in place of 10.4 mgof bis(cyclopentadienyl)ruthenium (II) and the reaction time was set to6 hours, 52.6 g (content: 5.6 wt. %) of the organic layer containingmethyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was83%.

Example 12

To 5.4 g of sodium metaperiodate (NaIO₄) was added 16 g of water, andthe mixture was adjusted to an internal temperature of 0° C., followedby the addition of 11.4 mg of ruthenium (II) chloride hydrate. To thiswere added 2 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 10g of dichloroethane, and the mixture was stirred at an internaltemperature of 0° C. for 4 hours to effect reaction. After completion ofthe reaction, insoluble matter containing by-product sodium iodate wasremoved by filtration. The removed insoluble matter was washed withdichloroethane, and the washing solution was mixed with the filtratepreviously obtained. The filtrate after the mixing was subjected tophase separation, and the resulting organic layer washed with an aqueoussolution of sodium thiosulfate to give 26.8 g (content: 5.4 wt. %) ofthe organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 85%.

Example 13

In the same manner as described in Example 12, except that hexane of thesame weight was used in place of dichloroethane and the reaction timewas set to 10 hours, 36.4 g (content: 3.2 wt. %) of the organic layercontaining methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.The yield was 68%.

Example 14

In the same manner as described in Example 12, except that ethyl acetateof the same weight was used in place of dichloroethane, 37.0 g (content:3.5 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 76%.

Example 15

In the same manner as described in Example 12, except that methylisobutyl ketone of the same weight was used in place of dichloroethaneand the reaction time was set to 7 hours, 40.5 g (content: 3.3 wt. %) ofthe organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 79%.

Example 16

To 11.5 g of periodic acid (H₅IO₆) was added 33 g of water, and themixture was adjusted to an internal temperature of 0° C., followed bythe addition of 6.1 mg of ruthenium (IV) oxide hydrate. To this wereadded 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 41g of toluene, and the mixture was stirred at an internal temperature of0° C. for 12 hours to effect reaction. The reaction mixture wassubjected to phase separation, and the resulting organic layer waswashed with an aqueous solution of sodium thiosulfate to give 70.1 g(content: 4.6 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 91%.

Example 17

To 11.6 g of potassium metaperiodate (KIO₄) was added 33 g of water, andthe mixture was adjusted to an internal temperature of 0° C., followedby the addition of 6 mg of ruthenium (IV) oxide hydrate. To this wereadded 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 20g of toluene, and the mixture was stirred at an internal temperature of0° C. for 24 hours to effect reaction. After completion of the reaction,insoluble matter containing by-product potassium iodate was removed byfiltration. The removed insoluble matter was washed with toluene, andthe washing solution was mixed with the filtrate previously obtained.The filtrate after the mixing was subjected to phase separation, and theresulting organic layer washed with an aqueous solution of sodiumthiosulfate to give 59.3 g (content: 3.1 wt. %) of the organic layercontaining methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.The yield was 52%.

Example 18

To 11.8 g of lithium periodate hydrate (LiIO₄.2H₂O) was added 35 g ofwater, and the mixture was adjusted to an internal temperature of 0° C.,followed by the addition of 6 mg of ruthenium (IV) oxide hydrate. Tothis were added 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, 41 gof toluene, and 9 g of 60 wt. % nitric acid, and the mixture was stirredat an internal temperature of 0° C. for 30 hours to effect reaction.After completion of the reaction, insoluble matter containing by-productlithium iodate was removed by filtration. The removed insoluble matterwas washed with toluene, and the washing solution was mixed with thefiltrate previously obtained. The filtrate after the mixing wassubjected to phase separation, and the resulting organic layer washedwith an aqueous solution of sodium thiosulfate to give 78.5 g (content:3.4 wt. %) of the organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 76%.

Example 19

To 10.8 g of sodium periodate (NaIO₄) was added 33 g of water, and themixture was adjusted to an internal temperature of 0° C., followed bythe addition of 6 mg of ruthenium (IV) oxide hydrate. To this were added4.1 g oftrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acidand 21 g of toluene, and the mixture was stirred at an internaltemperature of 0° C. for 23 hours to effect reaction. After completionof the reaction, insoluble matter containing by-product sodium iodatewas removed by filtration. The removed insoluble matter was washed withtoluene, and the washing solution was mixed with the filtrate previouslyobtained. The filtrate after the mixing was subjected to phaseseparation, and the resulting organic layer washed with an aqueoussolution of sodium thiosulfate to give 56.7 g (content: 2.0 wt. %) ofthe organic layer containingtrans-3,3-dimethyl-2-formylcyclopropanecarboxylic acid. The yield was35%.

Example 20

To 10.8 g of sodium periodate (NaIO₄) was added 33 g of water, and themixture was adjusted to an internal temperature of 0° C., followed bythe addition of 9.1 mg of ruthenium (III) chloride hydrate. To this wereadded 4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 41g of toluene, and the mixture was stirred at an internal temperature of0° C. for 18 hours to effect reaction. After completion of the reaction,insoluble matter containing by-product sodium iodate was removed byfiltration. The removed insoluble matter was washed with toluene, andthe washing solution was mixed with the filtrate previously obtained.The filtrate after the mixing was subjected to phase separation, and theresulting organic layer washed with an aqueous solution of sodiumthiosulfate to give 57.7 g (content: 5.6 wt. %) of the organic layercontaining methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.The yield was 91%.

Example 21

To 10.8 g of sodium periodate (NaIO₄) was added 33 g of water, and themixture was adjusted to an internal temperature of 0° C., followed bythe addition of 6 mg of ruthenium (IV) oxide hydrate. To this were added4.1 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate and 41g of toluene, and the mixture was stirred at an internal temperature of0° C. for 12 hours to effect reaction. After completion of the reaction,insoluble matter containing by-product sodium iodate was removed byfiltration. The removed insoluble matter was washed with toluene, andthe washing solution was mixed with the filtrate previously obtained.The filtrate after the mixing was subjected to phase separation, and theresulting organic layer washed with an aqueous solution of sodiumthiosulfate to give 70.5 g (content: 4.6 wt. %) of the organic layercontaining methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.The yield was 92%.

Example 22

To 44.4 g of sodium paraperiodate (Na₂H₃IO₆) recovered in Example 1 wasadded 203 g of water and at an internal temperature of 0° C. was added17.2 g of 60 wt. % nitric acid, giving an aqueous solution containingsodium metaperiodate (NaIO₄). At the same temperature, 32.4 mg ofruthenium (III) chloride hydrate, 14.2 g of methyltrans-3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylate, and144 g of toluene were added, and 1.7 g of sodium metaperiodate (NaIO₄)was further added. The mixture was stirred for 25.5 hours to effectreaction. After completion of the reaction, 2.4 g of isopropyl alcoholwas added to reduce the remaining sodium metaperiodate (NaIO₄), followedby the addition of a 20 wt. % aqueous solution of sodium carbonate forneutralization.

At an internal temperature of 70° C. was added 0.2 g of active carbon,and the mixture was stirred for about 30 minutes, followed by filtrationat the same temperature. The filtrate was left at rest and thensubjected to phase separation to give an organic layer containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate and an aqueous layercontaining by-product sodium iodate and/or iodic acid. The organic layerwas washed with an aqueous solution of sodium thiosulfate, followed byconcentration under reduced pressure to give 27.5 g (content: 38.5 wt.%) of the concentrated residue containing methyltrans-3,3-dimethyl-2-formylcyclopropanecarboxylate. The yield was 87%.

INDUSTRIAL APPLICABILITY

According to the present invention,3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivatives can beproduced in an industrially advantageous manner without using highlytoxic osmium tetroxide or ozone having a tendency to need large-scaleequipment. Further, the iodic acid compounds formed as by-products inthe reaction can be recovered as periodic acid compounds and therecovered periodic acid compounds can be reused in the presentinvention, so that the production process of the present invention isadvantageous from an economical point of view and from the viewpoint ofenvironmental burden.

1. A process for the production of a3,3-dimethyl-2-formylcyclopropanecarboxylic acid compound of formula(2):

wherein R is hydrogen, alkyl which may be substituted with asubstituent(s) which are halogen atoms, alkoxy groups, aryloxy groups oraralkyloxy groups, aryl which may be substituted with a substituent(s)which are the above alkyl, alkoxy, aryloxy or aralkyloxy, or aralkylwhich are composed of the above alkyl groups and the above aryl groups,which process comprises reacting a3,3-dimethyl-2(2-methyl-1-propenyl)cyclopropanecarboxylic acid compoundof formula (1):

wherein R is as defined above, with a periodic acid compound in thepresence of a ruthenium compound, wherein an iodic acid compoundproduced as a by-product in the reaction of the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acid compoundof formula (1) and the periodic acid compound is converted into andrecovered as a periodic acid compound, and the recovered periodic acidcompound is reused in the above reaction.
 2. The process for theproduction of the 3,3-dimethyl-2-formylcyclopropanecarboxylic acidcompound according to claim 1, wherein the periodic acid compoundexhibits acidic property in its aqueous solution.
 3. The process for theproduction of the 3,3-dimethyl-2-formylcyclopropanecarboxylic acidcompound according to claim 1, wherein the reaction is carried out inthe presence of a mixture of water and a water-immiscible organicsolvent.
 4. The process for the production of the3,3-dimethyl-2-formylcyclopropanecarboxylic acid compound according toclaim 1, wherein the ruthenium compound is ruthenium metal, a rutheniumoxide, a ruthenium halide, a ruthenium complex, or a perruthenate. 5.The process for the production of the3,3-dimethyl-2-formylcyclopropanecarboxylic acid compound according toclaim 1, wherein the amount of periodic acid compound used is 2 to 3moles, per mol of the3,3-dimethyl-2-(2-methyl-1-propenyl)cyclopropanecarboxylic acid compoundof formula (1).